This study seeks to evaluate the role of glucagon and insulin receptors in the pathogenesis of diabetes and related disorders of carbohydrate metabolism. The binding of glucagon to hepatic plasma membranes and glucagon-stimulated adenylate cyclase activity will be studied in a) streptozotocin-induced diabetic rats before and after treatment with insulin; b) glucocorticoid-induced glucose intolerance as observed in dexamethasone treated rats; c) in somatostatin-induced hypersensitivity to glucagon; and d) in hyperglucagonemic rats receiving repeated physiologic or pharmacologic doses of glucagon. In each of these studies, the effects of the various conditions on glucagon binding and glucagon stimulation of adenylate cyclase activity will be compared. In other studies we will examine whether changes in insulin binding to peripheral monocytes correlate with changes in the action of insulin in intact human subjects. Insulin action will be determined by the insulin clamp technique in which insulin is infused to achieve physiologic hyperinsulinemia while a variable servo-controlled glucose infusion is administered to maintain euglycemia. Studies correlating insulin binding and insulin action will be undertaken in a) obese subjects before and after starvation and refeeding; b) non-obese patients with juvenile-onset insulin dependent diabetes, and maturity-onset non-insulin dependent diabetes; c) patients with hypercorticism induced by short-term (3 day) dexamethasone administration, and d) patients with growth hormone deficiency, before and after replacement therapy.